A genetic mutation caused by ultraviolet light is likely the driving force behind millions of human skin cancers, according to researchers at the Stanford University School of Medicine. The mutation occurs in a gene called KNSTRN, which is involved in helping cells divide their DNA equally during cell division. Genes that cause cancer when mutated are known as oncogenes. Although KNSTRN hasn't been previously implicated as a cause of human cancers, the research suggests it may be one of the most commonly mutated oncogenes in the world. "This previously unknown oncogene is activated by sunlight and drives the development of cutaneous squamous cell carcinomas," said Paul Khavari, M.D., Ph.D., the Carl J. Herzog Professor in Dermatology in the School of Medicine and Chair of the Department of Dermatology. "Our research shows that skin cancers arise differently from other cancers, and that a single mutation can cause genomic catastrophe." Cutaneous squamous cell carcinoma is the second most common cancer in humans. More than 1 million new cases are diagnosed globally each year. The researchers found that a particular region of KNSTRN is mutated in about 20 percent of cutaneous squamous cell carcinomas and in about 5 percent of melanomas. A paper describing the research was published online on September 7, 2014 in Nature Genetics. Dr. Khavari, who is also a member of the Stanford Cancer Institute and Chief of the dermatology service at the Veterans Affairs Palo Alto Health Care System, is the senior author of the paper. Postdoctoral scholar Carolyn Lee, M.D., Ph.D., is the lead author. Drs. Lee and Khavari made the discovery while investigating the genetic causes of cutaneous squamous cell carcinoma. They compared the DNA sequences of genes from the tumor cells with those of normal skin and looked for mutations that occurred only in the tumors.
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